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Adaptive Responses as Mechanisms of Resistance to BRAF Inhibitors in Melanoma

1
Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden
2
Karolinska University Hospital Solna, 171 76 Stockholm, Sweden
3
School of Pharmacy and Biomedical Sciences, Curtin University, Perth 6845, Australia
4
Curtin Health Innovation Research Institute, Faculty of Health Sciences, Curtin University, Bentley, WA 6102, Australia
5
Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
6
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(8), 1176; https://doi.org/10.3390/cancers11081176
Received: 2 July 2019 / Revised: 8 August 2019 / Accepted: 9 August 2019 / Published: 14 August 2019
(This article belongs to the Special Issue Oncogenic Forms of BRAF as Cancer Driver Genes)
PDF [1545 KB, uploaded 14 August 2019]
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Abstract

: The introduction of v-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitors in melanoma patients with BRAF (V600E) mutations has demonstrated significant clinical benefits. However, rarely do tumours regress completely. Frequently, the reason for this is that therapies targeting specific oncogenic mutations induce a number of intrinsic compensatory mechanisms, also known as adaptive responses or feedback loops, that enhance the pro-survival and pro-proliferative capacity of a proportion of the original tumour population, thereby resulting in tumour progression. In this review we will summarize the known adaptive responses that limit BRAF mutant therapy and discuss potential novel combinatorial therapies to overcome resistance.
Keywords: BRAF/melanoma/adaptive responses/resistance BRAF/melanoma/adaptive responses/resistance
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Saei, A.; Eichhorn, P.J.A. Adaptive Responses as Mechanisms of Resistance to BRAF Inhibitors in Melanoma. Cancers 2019, 11, 1176.

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